Among the most studied spontaneous model strains are the NZB/W F1 and MRL/Lpr strains. The NZB/W mice develop severe glumeronephritis and anti-dsDNA antibodies without other clinical or serological manifestations of lupus. Anti-Sm/RNP antibodies are absent. A week IFN signature can be found at later stages of disease.

MRL/lpr mice develop disease with anti-Sm and anti-DsDNA/chromatin autoantibodies. MRL/lpr mice do not develop anti-RNP antibodies. No IFN signature can be found in this model.